Monoclonal antibodies (MAbs) will be produced to feline leukemia virus (FeLV) isolates. The MAbs will be used therapeutically in both serotherapy and in ex vivo immune absorption protocols to treat cats bearing experimentally induced, or naturally occurring leukemia, lymphoma, or sarcoma. Cats are excellent candidates for MAb serotherapy because antibody mediates immune resistance to virus infection and leukemia. MAbs injected into tumor-bearing animals are therefore expected to mimic some effects of cat antibodies found in tumor resistant individuals. Treatment protocols developed will have relevance for similar therapies in other non-inbred species. Considerable variation has been detected within FeLV proteins of viruses isolated from different cat tumors. These individual epitopes will be mapped to facilitate the choice of appropriate MAbs to develop enzyme-linked assays for circulating virus proteins. After development these assays will be applied to sera generated from cats treated by methods proposed here, and to a large variety of stored sera, to determine circulating virus antigen burdens in virus-exposed and tumor bearing cats. MAbs selected for therapeutic applications will be pooled on the basis of biological characteristics (e.g. cytotoxicity with cat complement) and of broad reactivity to several FeLV isolates. These MAb pools will be tested for their capacity to abrogate persistent retrovirus infection and/or to induce tumor regression in virus-exposed specific pathogen free cats. Therapeutically useful MAb secreting hybridomas will provide reproducible reagents on a large scale for clinical trials with naturally occurring leukemias. Ex vivo immune absorption using S. aureus is therapeutically effective for cat leukemia, probably because it reduces the circulating virus-antibody complex burdens of tumor-bearing cats thereby facilitating host immunity. MAbs selected for their reactivity with circulating tumor or virus antigens will be immobilized on absorption columns, and the effects of treatment of cats bearing naturally occurring leukemias will be compared using normal columns and MAb coated columns.